Few prospective studies of progressive of peripheral vascular disease (PVD) caused by atherosclerosis exist and no large studies have used objective methods to evaluate disease progression. Elevation of plasma homocysteine (HC) is an independent risk factor for PVD. Recent studies from our group demonstrated an important relationship between elevated plasma HC and rapid progression of PVD. This is of interest because of the ability to therapeutically lower elevated plasma HC with folic acid, which is without known toxicity. The project proposed is a blinded prospective study to elevate progression of atherosclerotic lower extremity (LED) and cerebrovascular disease (CVD) together referred to as PVD in patients with symptomatic PVD. The study will examine the influence of plasma (HC) on progression of PVD in patients in whom risk factors for atherosclerosis have been meticulously characterized. The two specific hypotheses to be tested are: 1. More patients with symptomatic PVD and elevated plasma HC will have progression of PVD than patients with symptomatic PVD and normal plasma HC. 2. Patients with symptomatic PVD and elevated plasma HC will have a more rapid rate of progression of PVD than patients with normal plasma HC. The primary outcome variables will be lower extremity arterial obstruction as assessed by ankle brachial systolic pressure index (ABI) and carotid artery stenosis as determined by duplex scanning. Secondary outcome variables include vascular death, need for vascular surgery, and clinical events indicating disease progression including stroke, transient ischemic attacks, gangrene, and ischemic rest pain. All primary and secondary outcome variables will be assessed in blinded fashion. The study will require five years; two years for enrollment of 400 patients with PVD, one third of whom will have elevated plasma HC, and three years for patient data collection regarding progression of atherosclerosis. All patients will receive standardized best medical and surgical care for PVD under the direction of the investigators. This study is important because folic acid has been demonstrated to reliably lower elevated plasma HC. A beneficial effect of folate may establish this agent as the first effective preventive treatment for atherosclerosis which is free of toxic side effects and does not involve major changes in life/dietary habits.